Asymptomatic Infection? Another Reason to Consider Monkeypox a Disease of Public Health Concern
Authors: Stuart N. Isaacs
Journal: Annals of Internal Medicine (2022)

EditorialsOctober 2022Asymptomatic Infection? Another Reason to Consider Monkeypox a Disease of Public Health ConcernFREEStuart N. Isaacs, MDStuart N. Isaacs, MDDivision of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, and Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PennsylvaniaAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M22-2457 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The current worldwide outbreak of disease caused by the monkeypox virus is unprecedented. Monkeypox virus was first found to cause disease in humans about 50 years ago, during the time of the intensified smallpox eradication program sponsored by the World Health Organization (WHO) (1). At that time, it was described as "a rare zoonotic infection, of little public health significance compared with other infectious diseases in central and western Africa …" (2). People were infected by contact with infected animals. Occasional human-to-human transmission occurred, typically within a household. Long chains of human-to-human transmission were rare. When human-to-human transmission occurred, the disease in the contact was usually milder, and previous smallpox vaccination further reduced disease manifestations (2). Routine smallpox vaccination, which also protected against monkeypox disease, ended when smallpox was declared eradicated in 1980 (3). At the time, it was deemed that the risk of continued use of the historical smallpox vaccine in Africa to prevent monkeypox was greater than the benefit. However, it was clear to scientists and epidemiologists that monkeypox needed to be monitored (2). Indeed, 30 years after cessation of smallpox vaccination, incidence of human monkeypox cases in central Africa was 20 times higher than during WHO surveillance of central Africa in the 1980s (4).In recent years, monkeypox cases outside endemic countries in Africa were related to travelers from an endemic country, and human-to-human transmission was rare. Before the current worldwide outbreak, the largest outbreak of monkeypox outside Africa occurred in the United States in 2003 (5). That outbreak of 72 confirmed or probable cases was related to contact with prairie dogs that had been accidentally infected at an animal distribution center that was also housing exotic rodents from Ghana. Of note, there was no evidence of human-to-human transmission, and the outbreak lasted about 2 months.At the time of this writing, the WHO has declared the current monkeypox outbreak—which involves more than 31 000 cases in more than 80 countries—to be a public health emergency of international concern. This unprecedented outbreak is due to continuous human-to-human transmission of the virus, predominantly in men who have sex with men (MSM). However, spread outside this social network will happen. In their article, Ferré and colleagues report the detection of monkeypox virus in anorectal swabs from asymptomatic MSM in a sexually transmitted infection screening program in Paris, France (6). The group retrospectively performed poxvirus polymerase chain reaction (PCR) testing on swabs from 200 asymptomatic MSM who were negative for Neisseria gonorrhoeae and Chlamydia trachomatis. They found 13 (6.5%) whose PCR results were positive for monkeypox virus. Two of these 13 later developed symptoms of monkeypox. Although it is not yet clear whether the positive PCR result represents the presence of infectious virus, it will not be surprising if it is present because the possibility of asymptomatic infections is not a new finding. However, it raises the question of whether asymptomatic or subclinical infections are contributing to the current worldwide outbreak.Studies in Africa in the 1980s reported by Jezek and Fenner provide evidence that the vast majority of monkeypox cases in unvaccinated people were symptomatic, and approximately 30% of cases may have been subclinical (2). This finding was based on serologic testing in a small number of unvaccinated people (mostly children) who had known exposure to a person in their household or by close contact with playmates. Although this evidence relies on monkeypox virus–specific serology, there may be stronger evidence of asymptomatic infection with variola virus. Sarkar and colleagues cultured the throats of 328 family contacts of 52 smallpox case patients (7). They were able to grow variola virus from the throat culture in 34 contacts (10%). Eighteen of these contacts were vaccinated, and 16 were unvaccinated. Four of the 34 patients with positive culture results went on to develop symptomatic smallpox disease. Interestingly, 3 of the 4 who developed symptoms were previously vaccinated. This study also provides evidence of protection from prior vaccination, given that approximately 5% of the contacts with negative culture results were unvaccinated, whereas 47% of those with positive culture results were unvaccinated. In another cohort of 52 family members exposed to a case of smallpox, Sarkar and colleagues were able to culture variola virus in 5 (10%) persons (8). All had evidence of prior vaccination, and serial throat cultures were positive for 6 to 21 days. One of the 5 developed symptoms of smallpox.The role of subclinical or asymptomatic infection in transmission of monkeypox virus or variola virus is not known. Historically, transmission of these viruses was thought to be greatest when the rash was present. The presence of virus in throat cultures in asymptomatic people was believed to be of little or no epidemiologic importance given that the successful eradication of smallpox was due in part to the ability to always identify a source patient (9). However, the current worldwide monkeypox epidemic and the mode of human-to-human transmission may provide evidence that asymptomatic or preclinical spread can occur. Because of this possibility, an expanded ring vaccination strategy as one of the public health responses in the communities at highest risk is likely needed to help control the outbreak. However, we should keep in mind that control of this outbreak will only be successful if vaccination is used along with other public health interventions, including identifying and isolating cases, making treatment available, and educating the public to decrease the risk for potential exposure while community spread is at a high level.References1. Ladnyj ID, Ziegler P, Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bull World Health Organ. 1972;46:593-7. [PMID: 4340218] MedlineGoogle Scholar2. Jezek Z, Fenner F. Human Monkeypox. Monographs in Virology. 1988;17. doi:10.1159/isbn.978-3-318-04039-5 CrossrefGoogle Scholar3. Global Commission for the Certification of Smallpox Eradication; World Health Organization. The global eradication of smallpox: final report of the Global Commission for the Certification of Smallpox Eradication, Geneva, December 1979. World Health Organization; 1980. Google Scholar4. Rimoin AW, Mulembakani PM, Johnston SC, et al. Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo. Proc Natl Acad Sci U S A. 2010;107:16262-7. [PMID: 20805472] doi:10.1073/pnas.1005769107 CrossrefMedlineGoogle Scholar5. Reed KD, Melski JW, Graham MB, et al. The detection of monkeypox in humans in the Western Hemisphere. N Engl J Med. 2004;350:342-50. [PMID: 14736926] CrossrefMedlineGoogle Scholar6. Ferré VM, Bachelard A, Zaidi M, et al. Detection of monkeypox virus in anorectal swabs from asymptomatic men who have sex with men in a sexually transmitted infection screening program in Paris, France. Ann Intern Med. 2022;175:1491-2. doi:10.7326/M22-2183 LinkGoogle Scholar7. Sarkar JK, Mitra AC, Mukherjee MK, et al. Virus excretion in smallpox. 2. Excretion in the throats of household contacts. Bull World Health Organ. 1973;48:523-7. [PMID: 4359679] MedlineGoogle Scholar8. Sarkar JK, Mitra AC, Mukherjee MK. Duration of virus excretion in the throat of asymptomatic household contacts of smallpox patients. Indian J Med Res. 1974;62:1800-3. [PMID: 4377667] MedlineGoogle Scholar9. Fenner F, Henderson DA, Arita I, et al. Smallpox and its eradication. World Health Organization; 1988. Google Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, and Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PennsylvaniaDisclaimer: The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the University of Pennsylvania, the U.S. Department of Veterans Affairs, or the U.S. government.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-2457.Corresponding Author: Stuart N. Isaacs, MD, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, 319 Johnson Pavilion, Philadelphia, PA 19104; e-mail, [email protected]upenn.edu.This article was published at Annals.org on 16 August 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDetection of Monkeypox Virus in Anorectal Swabs From Asymptomatic Men Who Have Sex With Men in a Sexually Transmitted Infection Screening Program in Paris, France Valentine Marie Ferré , Antoine Bachelard , Meryem Zaidi , Laurence Armand-Lefevre , Diane Descamps , Charlotte Charpentier , and Jade Ghosn Metrics October 2022Volume 175, Issue 10Page: 1485-1486KeywordsGlobal healthInfectious diseasesMale male sexual contactMonkeypoxPrevention, policy, and public healthSmallpoxVaccines ePublished: 16 August 2022 Issue Published: October 2022 PDF downloadLoading ...